Glomerulonephritis/nephritic syndrome

• The term ‘nephritic’ refers to glomerulonephritis (i.e. inflammation in the glomerulus), characterised by blood and protein present in the urine dip and often reduced kidney function. 
• Clinical features:

  • Proteinuria (typically less than nephrotic syndrome)
  • Haematuria - micro or macroscopic. Can cause red cell casts.
  • Hypertension - due to salt and water retention. Activation of RAAS.
  • Renal impairment and oliguria
  • Pyuria - inflammation that can form white cell casts in the urine that can be examined under microscopy
• Chronicity of disease is important in nephritic syndrome. If symptoms occur and renal function declines over days or weeks, it can be classified as acute glomerulonephritis. If the symptoms occur over months to years with little reduction in kidney function, then it is chronic glomerulonephritis.
• Rapidly progressive glomerulonephritis (synonymous with crescentic GN) is a sub-classification of acute glomerulonephritis which is associated with crescents on renal biopsy.

  • 50% decline in kidney function over 3 months or less
  • Not a single disease process but describes glomerulonephritis which can present very acutely
  • Presence of crescents on histology
• The causes of acute glomerulonephritis can also be subclassified into three main pathologies: immune complex disease, vasculitis (often pauci-immune) and anti-GBM associated diseases.
• Immune complex diseases:

  • activation of the complement system by immune complexes that deposit on the glomerular capillaries
  • Inflammation and damage
  • Low C3 and/or C4 levels
  • Causes - post infectious glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) and IgA GN
• Post streptococcal GN:

  • Immune complex disease
  • Due to group A streptococcal infection
  • Presents 2-3 weeks after infection
  • Low C3/4
  • Positive anti-streptolysin titre
  • Renal biopsy required in adults
  • Most common cause of GN in children
  • usually self limiting, supportive management
• IgA glomerulonephritis:

  • Most common primary chronic glomerular disease worldwide
  • Deposition of IgA immunoglobulins within the glomeruli
  • Haematuria hours to days after recent respiratory tract infection
  • Raised plasma IgA
  • IgA deposition with mesangial expansion on renal biopsy
  • ACE inhibitors
  • High dose prednisolone
  • Immunosuppression
• Membranoproliferative glomerulonephritis (MPGN):

  • Typically affects patients under 30
  • Basement membrane and mesangial thickening & proliferation on light microscopy with 'tram tracking' due to GBM expansion
  • Associated with haematological malignancies, autoimmune diseases and chronic viral infections (Hep C)
  • Treat underlying cause
  • Children - corticosteroids
  • Adults - antiplatelets
  • Kidney transplant for ESRD
• Vasculitis can be split into small, medium or large vessel disease or be subclassified according to their immunofluorescence pattern on histology.
• Diseases typically associated with renal vasculitis:

  • Granulomatosis with polyangiitis (GPA)
  • Eosinophilic granulomatosis with polyangiitis (eGPA)
  • Microscopic polyangiitis (MPA)
  • These are associated with ANCA antibodies
  • Treatment involves high dose immunosuppression
• Anti-GBM disease:

  • Immune mediated pathology involving antibodies directed against glomerular basement membrane antigens
  • Targets type IV collagen
  • Antigens located in the glomeruli and alveoli of the lungs
  • Kidneys - nephritic syndrome
  • Lungs - alveolar haemorrhage presenting with haemoptysis
  • Goodpasture's syndrome = kidney and lungs affected
  • Accounts for 10% of RPGN
• Investigations for Anti-GBM disease:

  • Immunochemistry - IgG deposits along the basement membrane of the glomerulus
  • Antibodies - Anti-GBM antibodies
• Management of anti-GBM disease:

  • High dose immunosuppression - IV prednisolone
  • Cyclophosphamide
  • Plasmapheresis
  • Renal replacement therapy/transplant